Mathematical model of photobiomodulation on cytochrome c oxidase

Photobiomodulation (PBM) is an approach utilizing light to trigger of beneficial effects in biological tissues. The leading hypothesis of PBM states light could dissociate the nitric oxide from cytochrome c oxidase (COX), complex IV in mitochondria, and result in an increased oxygen consumption rate, ATP production, and other downstream effects. However, this hypothesis remains elusive due to difficulties in monitoring intracellular light-biomolecule interactions. The mathematical model describing the light effect on COX was proposed from previous established COX models and tested by simulating the previous experiments of state 3 respiration rates under 442, 532, 650, and 980 nm treatments. Our simulation results suggest the activating PBM effect can be explained as the result of nitric oxide (NO) photodissociation and low environmental NO sustained by light-induced superoxide, preventing NO from rebinding to COX. At 442 and 532 nm, the proposed model fits with the dose-response curve, while inconsistency of high doses at 650 and 980 nm suggests that other mechanisms, instead of the NO photodissociation alone, might contribute to the PBM effect in red and infrared light.